Polyene macrolide antibiotics represent an important class of compounds which have found wide utility in the pharmaceutical field, especially because of their antibiotic properties. Many of the currently identified polyene macrolide antibiotics are illustrated in FIG. 26. The compounds are uniquely characterized by a large lactone ring which includes a chain of conjugated double bonds, comprising from three to seven such conjugated double bonds.
Although amphotericin B is the most well-known of the polyene macrolide antibiotics, other polyene antibiotics such as faeriefungin, nystatin, natamycin, hamycin, aureofungin and candicidin, have been known and used clinically for many years. More recently, dermostatin has been found to have activity against fungi and to be useful in the treatment of certain fungal infections.
The compounds are generally classified according to the number of conjugated double bonds in the structure and are correspondingly referred to as trienes, tetraenes, pentaenes, hexaenes and heptaenes, as illustrated in FIG. 26. The compounds all have high molecular weight, such as from about 700 to about 1200, and may be referred to as macrocyclic lactones, which have an amino sugar glycoside of a macrolide nucleus that possess a chromophore of 3 to 7 conjugated double bonds.
Because the polyene macrolide antibiotics conventionally are produced by cultivation of various organisms, it is often the case that they exist as complexes which contain more than one dominant macrolide structure. For example, dermostatin (or dermostatin complex) is known in actuality to contain two dominant structures which have been identified and named dermostatin A and dermostatin B. They are both carbonyl conjugated polyene macrolide antimicrobial agents that differ only slightly in structure. Heretofore, no preparatory procedure has existed to isolate dermostatin A and dermostatin B from the dermostatin complex in purified forms.
Similarly, mycoticin, it has now been discovered, is comprised of three distinct compounds now known as mycoticin A, mycoticin B and mycoticin C. There also has not been available a preparatory procedure for isolating and purifying those individuals components of mycoticin complex. A similar need for a general separation and purification procedure exists with respect to other polyene macrolide antibiotics as well.